Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.
Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.
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DOI：
10.1111/pcmr.12284
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发表时间：
2014-11
影响因子：
4.3
通讯作者：
Le Poole IC
中科院分区：
文献类型：
--
作者：
Eby JM;Kang HK;Klarquist J;Chatterjee S;Mosenson JA;Nishimura MI;Garrett-Mayer E;Longley BJ;Engelhard VH;Mehrotra S;Le Poole IC
为了产生自发性表皮色素脱失的小鼠模型，将在T细胞上表达人源性酪氨酸酶反应性T细胞受体和匹配的HLA-A2转基因的亲本h3 TA 2小鼠与具有表皮内黑素细胞的角蛋白14启动子驱动的干细胞因子转基因（K14-SCF）小鼠杂交。在由此产生的Vitesse小鼠中，自发的皮肤色素脱失先于对称的和明显分界的灰毛斑块。尽管SCF转基因单独决定了更大的视黄酸受体相关孤儿受体γ（RORγt）+ T细胞区室，但这些细胞在Vitesse小鼠中显示出显著增加的IL-17表达。与患者皮肤相似，与K14-SCF小鼠相比，调节性T细胞的丰度较低，除了逐渐出现的色素沉着皮肤斑块。观察到的细微的色素沉着可能反映了与皮肤浸润的黑素细胞反应性T细胞共存的弹性黑素细胞。在SCF转基因背景下开发的不同TCR转基因白癜风模型中发现了类似的再色素沉着病变，支持SCF在再色素沉着中的作用。
To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human-derived, tyrosinase-reactive T cell receptor on T cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor-related orphan receptor gamma (RORγt)+ T cell compartment, these cells displayed markedly increased IL-17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared to K14-SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that co-exist with skin-infiltrating, melanocyte-reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.